Diazoxide blocks or reduces microgliosis when applied prior or subsequent to motor neuron injury in mice.

Diazoxide (DZX), an anti-hypertonic and anti-hypoglycemic drug, was shown to have anti-inflammatory effects in several injured cell types outside the central nervous system. In the brain, the neuroprotective potential of DZX is well described, however, its anticipated anti-inflammatory effect after acute injury has not been systematically analyzed. To disclose the anti-inflammatory effect of DZX in the central nervous system, an injury was induced in the hypoglossal and facial nuclei and in the oculomotor nucleus by unilateral axonal transection and unilateral target deprivation (enucleation), respectively. On the fourth day after surgery, microglial analysis was performed on tissue in which microglia were DAB-labeled and motoneurons were labeled with immunofluorescence. DZX treatment was given either prophylactically, starting 7 days prior to the injury and continuing until the animals were sacrificed, or postoperatively only, with daily intraperitoneal injections (1.25 mg/kg; in 10 mg/ml dimethyl sulfoxide in distilled water). Prophylactically + postoperatively applied DZX completely eliminated the microglial reaction in each motor nuclei. If DZX was applied only postoperatively, some microglial activation could be detected, but its magnitude was still significantly smaller than the non-DZX-treated controls. The effect of DZX could also be demonstrated through an extended period, as tested in the hypoglossal nucleus on day 7 after the operation. Neuronal counts, determined at day 4 after the operation in the hypoglossal nucleus, demonstrated no loss of motor neurons, however, an increased Feret's diameter of mitochondria could be measured, suggesting increased oxidative stress in the injured cells. The increase of mitochondrial Feret's diameter could also be prevented with DZX treatment.

Nicotine effects on muscarinic receptor-mediated free Ca[Formula: see text] level changes in the facial nucleus following facial nerve injury.

It was suggested that muscarinic, and nicotinic receptors increase free Ca[Formula: see text] levels in the facial nerve nucleus via various channels following facial nerve injury. However, intracellular Ca[Formula: see text] overload can trigger either necrotic or apoptotic cell death. It is assumed that, following facial nerve injury, the interactions of nicotinic and muscarinic acetylcholine receptors in facial nerve nucleus may negatively regulate free Ca[Formula: see text] concentrations in the facial nerve nucleus, which provide important information for the repair and regeneration of the facial nerve. The present study investigated the regulatory effects of nicotine on muscarinic receptor-mediated free calcium ion level changes in the facial nucleus in a rat model of facial nerve injury at 7, 30, and 90 days following facial nerve injury using laser confocal microscopy. The dose-dependent regulation of nicotine on muscarinic receptor-mediated free calcium ion level changes in the facial nucleus may decrease the range of free Ca[Formula: see text] increases following facial nerve injury, which is important for nerve cell regeneration. It is concluded that the negative effects of nicotine on muscarinic receptors are related to the [Formula: see text] subtype of nicotinic receptors.

Mitochondrial Cyclophilin D as a Potential Therapeutic Target for Ischemia-Induced Facial Palsy in Rats.

Many studies have demonstrated that ischemia could induce facial nerve (FN) injury. However, there is a lack of a suitable animal model for FN injury study and thus little knowledge is available about the precise mechanism for FN injury. The aims of this study were to establish a reliable FN injury model induced by blocking the petrosal artery and to investigate whether dysfunctional interaction between cyclophilin D (CypD) and mitochondrial permeability transition pore (MPTP) can mediate cell dysfunction in ischemic FN injury. The outcomes of ischemia-induced FN injury rat model were evaluated by behavioral assessment, histological observation, electrophysiology, and electron microscopy. Then the levels of CypD and protein that forms the MPTP were evaluated under the conditions with or without the treatment of Cyclosporin A (CsA), which has been found to disrupt MPTP through the binding of CypD. The blocking of petrosal artery caused significant facial palsy signs in the ischemia group but not in the sham group. Furthermore, ischemia can induce the dysfunction of facial nucleus neurons and destruction of the myelin sheath and increase the protein levels of CypD and MPTP protein compared with sham group. Interestingly, treatment with CsA significantly improved neurological function and reversed the ischemia-induced increase of CypD and MPTP proteins in ischemia group. These results demonstrated that blocking of petrosal artery in rats can induce FN injury and the mechanism may be related to the disruption of MPTP by CypD.